enalapril and Necrosis

Mercuric chloride (HgCl2) induces kidney damage, in part, through oxidative stress. A role for angiotensin II (Ang II) in pro-inflammatory events in a model of acute HgCl2-induced nephropathy was reported. Ang II is a potent oxidative stress inducer; however, its role in oxidative/anti-oxidative events in HgCl2-induced nephropathy remains unknown. The aim of this study was to determine the role of Ang II in the oxidative stress and renal infiltration of CD8(+) T-cells after an acute HgCl2 intoxication. Three groups of Sprague Dawley rats were treated with a single subcutaneous dose of 2.5 mg/kg HgCl2: for 3 days prior to and for 4 days after that injection, rats in one group received Losartan (30 mg/kg), in another group Enalapril (30 mg/kg) or normal saline in the last group. Two other groups of drug-treated rats received saline in place of HgCl2. A final group of rats received saline in place of HgCl2 and the test drugs. All treatments were via gastric gavage. At 96 h after the vehicle/HgCl2 injection, blood and kidney samples were harvested. Renal sections were homogenized for measures of malondialdehyde (MDA), reduced glutathione (GSH) and catalase activity. Frozen sections were studied for the presence of superoxide anion ([Formula: see text]) and CD8(+) T-cells. HgCl2-treated rats had increased interstitial and tubular expression of [Formula: see text], high levels of MDA, normal catalase activity and GSH content, increased levels of interstitial CD8(+) T-cells and an increased percentage of necrotic tubules. Anti-Ang II treatments diminished the HgCl2-induced increases in interstitial [Formula: see text], CD8(+) T-cells and tubular damage and increased catalase and GSH expression above that due to HgCl2 alone; the HgCl2-induced high MDA levels were unaffected by the drugs. These data provide new information regarding the potential role of Ang II in the oxidative stress and renal CD8(+) T-cell infiltration that occur during HgCl2 nephropathy.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Catalase; CD8-Positive T-Lymphocytes; Enalapril; Glutathione; Kidney; Kidney Diseases; Losartan; Male; Malondialdehyde; Mercuric Chloride; Necrosis; Oxidative Stress; Rats; Rats, Sprague-Dawley

A case of enalapril-induced acute hepatotoxicity with an unusual morphology is described. This morphology was characterized by macro- and microvesicular steatosis associated with neutrophil infiltration and Mallory bodies, occasionally with satellitosis. These alterations were most abundant in zone 1 of the periportal region, less common in zone 2 and rare in zone 3. There was also confluent periportal necrosis with sinusoidal fibrin deposits associated with intense ductal metaplasia and an infiltrate of inflammatory cells that included plasmocytes and a few eosinophils, as well as focal biliary damage. This morphology, that may be referred as "predominantly periportal steatohepatitis", was distinct from that associated with non-alcohol and alcohol-induced steatohepatitis, both initiated in acinar zone 3 and subsequently extended to other zones.

Topics: Acute Disease; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biopsy; Chemical and Drug Induced Liver Injury; Enalapril; Fatty Liver; Humans; Liver; Male; Necrosis; Neutrophil Infiltration

The effects of bradykinin were evaluated using the ACE inhibitor enalapril and the APP inhibitor, 2-mercaptoethanol alone and in combination in rats with experimental myocardial infarction. Myocardial infarction was produced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured by the TTC stain method. Lipid peroxide levels in serum and heart tissue were estimated by the methods developed by Yagi and Ohkawa et al., respectively. A lead II electrocardiogram was monitored throughout the experiment. With the combined inhibition of both the enzymes ACE and APP, a better cardioprotection was observed when compared to individual inhibition of the enzymes, suggesting the involvement of bradykinin during experimental myocardial infarction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Bradykinin; Coronary Vessels; Electrocardiography; Enalapril; Female; Heart Rate; Lipid Peroxides; Male; Mercaptoethanol; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Necrosis; Rats; Rats, Sprague-Dawley

To quantify the structural myocardial response when chronic NO blockade hypertension is treated with antihypertensive drugs.. Four groups of 10 male Wistar rats each were separated as follows: control, L-arginine-methyl-ester (NAME), L-NAME + angiotenisin-converting inhibitor (enalapril), L-NAME + calcium channel blocker (verapamil). All animals' blood pressure (BP) was measured weekly. After 40 days of experimentation the heart mass/body mass ratio (HBR) was determined, and the volume densities of the cardiac components were shown by stereology (Vv[c] for cardiomyocytes, Vv[i] for cardiac interstitium and the mean cross-sectional area of cardiomyocytes, a[c]).. Significant differences by comparison with the control group were: BP increased 71% and HBR increased 24% in the L-NAME group. Vv[c] was 15% smaller in L-NAME animals, while an increase of 11% occurred in the enalapril group and 7% in the verapamil group. Vv[i] increased 20% in the L-NAME group; however, it decreased 13% in the enalapril group and 10% in the verapamil group. a[c] Was 30% greater in the L-NAME group, 13.5% in the enalapril group and 8.5%, in the verapamil group. a[c] Was 12.5% smaller in the enalapril group and 16% smaller in the verapamil group when L-NAME rats were compared.. Stereology revealed an equivalent effect of enalapril and verapamil in reducing BP, cardiomyocyte hypertrophy and interstitial fibrosis in rats with NO synthesis blockade after six weeks of treatment.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Apoptosis; Blood Pressure; Calcium Channel Blockers; Cardiomegaly; Enalapril; Male; Necrosis; NG-Nitroarginine Methyl Ester; Rats; Rats, Wistar; Verapamil

Individually, both late reperfusion and early angiotensin converting enzyme (ACE) inhibitor treatment prevent infarct expansion after acute myocardial infarction.. To examine the effect and mechanism of early post-myocardial infarction ACE inhibitor treatment, when used in combination with late coronary artery reperfusion, on infarct expansion.. Sprague-Dawley rats underwent 8 h of coronary occlusion followed by permanent reperfusion. The treatment group received enalapril, started 1 h after coronary occlusion and continued for 13 days. A control group received placebo. Two weeks after acute myocardial infarction, hemodynamic, morphometric and histologic analyses were performed.. Hemodynamic parameters were similar in both groups (P = NS). Infarct size was similar in the ACE inhibitor and placebo treatment groups (44 +/- 4% compared with 39 +/- 4%, P = NS). Septal thickness was also similar in the two groups (2.8 +/- 0.3 mm compared with 2.7 +/- 0.3 mm, P = NS). The ACE inhibitor-treated group had thicker infarcts than those in the placebo-treated group (0.93 +/- 0.07 mm compared with 0.76 +/- 0.04 mm, P < 0.05) and these infarcts were less expanded (expansion index 1.17 +/- 0.12 compared with 1.57 +/- 0.12, P < 0.05). ACE inhibitor treatment was associated with hypertrophy of viable myocytes within the scar compared with placebo treatment (cell diameter 11.1 +/- 0.5 microns compared with 8.9 +/- 0.4 microns, P < 0.01).. Early post-myocardial infarction ACE inhibitor treatment enhances the benefits of late coronary reperfusion on infarct expansion. The benefits may be related to hypertrophy of still-viable myocytes within the infarcted zone.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Disease Models, Animal; Enalapril; Female; Hemodynamics; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Necrosis; Probability; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Survival Rate; Time Factors; Treatment Outcome

The inappropriate use of antihypertensive medications may cause hypotensive responses associated with organ failure. We describe a patient who developed nonocclusive splanchnic ischemia leading to death following the administration of enalapril to treat postoperative hypertension. The mechanisms and consequences of refractory hypotension induced by angiotensin-converting enzyme inhibitors are discussed.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arthritis, Rheumatoid; Colon; Enalapril; Fatal Outcome; Female; Humans; Hypertension; Ischemia; Multiple Organ Failure; Necrosis; Postoperative Complications; Splanchnic Circulation

To investigate the role of the renal medulla in early hypertension in spontaneously hypertensive rats (SHR), and to explore whether the attenuated increase of pressure induced by enalapril treatment is affected by chemical medullectomy.. Forty-four male SHR were studied from 5 to 18 weeks of age: 22 remained intact; 22 were medullectomized at 5.5 weeks of age with 2-bromoethylamine hydrobromide; 11 of each of these two groups were treated with enalapril from 6 to 12 weeks of age. Blood pressure, heart rate and body weight were recorded intermittently, and at 18 weeks renal function was also analysed.. The results indicate a protective effect of the renal medulla against severe pressure rises in SHR, although even when enalapril also lowered blood pressure in medullectomized SHR, persistent improvements of glomerular filtration rate and renal flow conductance occurred only in intact SHR. Furthermore, after enalapril treatment ended blood pressure rose to higher levels in medullectomized SHR, despite greater sodium-water losses.. The renal medulla seems to exert a protective role both during and after enalapril treatment.

Topics: Animals; Blood Pressure; Enalapril; Ethylamines; Glomerular Filtration Rate; Heart; Heart Rate; Hypertension; Kidney; Kidney Medulla; Male; Necrosis; Organ Size; Rats; Rats, Inbred SHR; Renal Circulation

Topics: Acute Disease; Aged; Enalapril; Fatal Outcome; Humans; Hypertension; Male; Necrosis; Pancreatitis

The effects of modulators of cytochrome P450 and reduced glutathione (GSH) on the hepatotoxicity of enalapril maleate (EN) were investigated in Fischer 344 rats. Twenty-four hours following the administration of EN (1.5 to 1.8 g/kg), increased serum transaminases (ALT and AST) and hepatic necrosis were observed. Pretreatment of the animals with pregnenolone-16 alpha-carbonitrile, a selective inducer of the cytochrome P450IIIA gene subfamily, enhanced EN-induced hepatotoxicity, whereas pretreatment with the cytochrome P450 inhibitor, cobalt protoporphyrin, reduced the liver injury. Depletion of hepatic non-protein sulfhydryls (NPSHs), an indicator of GSH, by combined treatment with buthionine sulfoximine (BSO) and diethyl maleate (DEM) produced marked elevations in serum transaminases by 6 hr after EN treatment. Administered on its own, EN decreased hepatic NPSH content and when combined with the BSO/DEM pretreatment, the liver was nearly completely devoid of NPSHs. Protection from EN-induced hepatotoxicity was observed in animals administered L-2-oxothiazolidine-4-carboxylic acid, a cysteine precursor. Together, these observations suggest the involvement of cytochrome P450 in EN bioactivation and GSH in detoxification. The results corroborate previous in vitro observations pertaining to the mechanism of EN-induced cytotoxicity towards primary cultures of rat hepatocytes. Although the doses of EN used in this study were far in excess of therapeutic doses, under certain circumstances, this metabolism-mediated toxicologic mechanism could form the basis for idiosyncratic liver injury in patients receiving EN therapy.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Biomarkers; Biotransformation; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Enalapril; Enzyme Induction; Glutathione; Inactivation, Metabolic; Liver; Liver Diseases; Male; Necrosis; Pregnenolone Carbonitrile; Protoporphyrins; Pyrrolidonecarboxylic Acid; Rats; Rats, Inbred F344; Sulfhydryl Compounds; Thiazoles; Thiazolidines